Down-regulation of AMPK/PPARδ signalling promotes endoplasmic reticulum stress-induced endothelial dysfunction in adult rat offspring exposed to maternal diabetes.

Aims: Exposure to maternal diabetes is associated with increased prevalence of hypertension in the offspring. The mechanisms underlying the prenatal programming of hypertension remain unclear. Because endoplasmic reticulum (ER) stress plays a key role in vascular endothelial dysfunction in hypertension, we investigated whether aberrant ER stress causes endothelial dysfunction and high blood pressure in the offspring of dams with diabetes.

Genetic variants of GRK4 influence circadian rhythm of blood pressure and response to candesartan in hypertensive patients.

: Genetic variants of coding genes related to blood pressure regulation participate in the pathogenesis of hypertension and determines the response to specific antihypertensive drugs. G protein-coupled receptor kinase 4 (GRK4) and its variants are of great importance in pathogenesis of hypertension. However, little is known about role of GRK4 variants in determine circadian rhythm of blood pressure and response to candesartan in hypertension.

LARP7 Protects Against Heart Failure by Enhancing Mitochondrial Biogenesis.

Background: Heart failure (HF) is among the leading causes of morbidity and mortality, and its prevalence continues to rise. LARP7 (La ribonucleoprotein domain family member 7) is a master regulator that governs the DNA damage response and RNAPII (RNA polymerase II) pausing pathway, but its role in HF pathogenesis is incompletely understood.

Methods: We assessed LARP7 expression in human HF and in nonhuman primate and mouse HF models.

Importance of extracellular vesicles in hypertension.

Hypertension affects approximately 1.13 billion adults worldwide and is the leading global risk factor for cardiovascular, cerebrovascular, and kidney diseases. There is emerging evidence that extracellular vesicles participate in the development and progression of hypertension.

Gastrin, via activation of PPARα, protects the kidney against hypertensive injury.

Hypertensive nephropathy (HN) is a common cause of end-stage renal disease with renal fibrosis; chronic kidney disease is associated with elevated serum gastrin. However, the relationship between gastrin and renal fibrosis in HN is still unknown. We, now, report that mice with angiotensin II (Ang II)-induced HN had increased renal cholecystokinin receptor B (CCKBR) expression.

The role of G protein-coupled receptor kinase 4 in cardiomyocyte injury after myocardial infarction.

Aims: G protein-coupled receptor kinase 4 (GRK4) has been reported to play an important role in hypertension, but little is known about its role in cardiomyocytes and myocardial infarction (MI). The goal of present study is to explore the role of GRK4 in the pathogenesis and progression of MI.

Methods And Results: We studied the expression and distribution pattern of GRK4 in mouse heart after MI.

AdipoRon, an adiponectin receptor agonist, protects contrast-induced nephropathy by suppressing oxidative stress and inflammation via activation of the AMPK pathway.

Background: Contrast-induced nephropathy (CIN), a complication caused by using contrast medium during diagnostic and interventional procedures, occurs frequently and lacks effective treatment. AdipoRon, the agonist of adiponectin receptors, has been shown to benefit many organs including the kidney. This study aimed to investigate the role of AdipoRon in treating CIN.

MiR-124-3p reduces angiotensin II-dependent hypertension by down-regulating EGR1.

Through previous literature studies, we found that miR-124-3p may be associated with hypertension. Therefore, we investigated the relationship between miR-124-3p and hypertension in Human Umbilical Vein Endothelial Cells (HUVECs) induced by angiotensin II (AngII). AngII-induced HUVECs model was constructed and the expression of miR-124-3p was detected by qRT-PCR.

Role of GRK4 in the regulation of the renal ETB receptor in hypertension.

The endothelin receptor type B (ETBR) regulates water and electrolyte balance and blood pressure, in part, by inhibiting renal sodium transport. Our preliminary study found that the ETBR-mediated diuresis and natriuresis are impaired in hypertension with unknown mechanism. Persistently increased activity of G protein-coupled receptor kinase 4 (GRK4), caused by increased expression or genetic variants (eg, GRKγ142V), impairs the ability of the kidney to excrete a sodium load, in part, by impairing renal dopamine D receptor function through persistent phosphorylation.

Association Between Delays in Mechanical Ventilation Initiation and Mortality in Patients With Refractory Cardiogenic Shock.

This study investigates the association between timing of mechanical ventilation initiation and mortality in patients with refractory cardiogenic shock.

Long Noncoding RNA Protects Against Cardiac Hypertrophy Through SUZ12 (Suppressor of Zeste 12 Protein Homolog)-Mediated Downregulation of MEF2A (Myocyte Enhancer Factor 2A).

Background: Long noncoding RNA (lncRNA) can regulate various physiological and pathological processes through multiple molecular mechanisms in cis and in trans. However, the role of lncRNAs in cardiac hypertrophy is yet to be fully elucidated.

Methods: A mouse lncRNA microarray was used to identify differentially expressed lncRNAs in the mouse hearts following transverse aortic constriction-induced pressure overload comparing to the sham-operated samples.

The relationship between neighborhood socioeconomic deprivation and telomere length: The 1999-2002 National Health and Nutrition Examination Survey.

Socioeconomically disadvantaged neighborhoods have been associated with poor health outcomes. Little is known about the biological mechanism by which deprived neighborhood conditions exert negative influences on health. Data from the 1999-2002 National Health and Nutrition Examination Surveys (NHANES) were used to assess the relationship between neighborhood deprivation index (NDI) and log-transformed leukocyte telomere length (LTL) via multilevel modeling to control for census tract level clustering.

Evaluation of the Effect of 5 QT-Positive Drugs on the JTpeak Interval - An Analysis of ECGs From the IQ-CSRC Study.

The JTpeak interval has been proposed as a new biomarker to demonstrate mixed ion channel effects, potentially leading to reduced late-stage electrocardiogram (ECG) monitoring for mildly QT-prolonging drugs. ECG waveforms from the IQ-CSRC study were used. Twenty healthy subjects were enrolled with 6 subjects on placebo and 9 subjects on each of 5 mildly QT-prolonging drugs - moxifloxacin, dofetilide, ondansetron, dolasetron, and quinine - and 1 negative drug, levocetirizine.

PM2.5 air pollution and cause-specific cardiovascular disease mortality.

Background: Ambient air pollution is a modifiable risk factor for cardiovascular disease, yet uncertainty remains about the size of risks at lower levels of fine particulate matter (PM2.5) exposure which now occur in the USA and elsewhere.

Methods: We investigated the relationship of ambient PM2.

[Impact of oxidative stress on renal dopamine D(1) receptor dysfunction in offspring of diabetic rat dams].

To explore the effects of oxidative stress on renal dopamine D(1) receptor dysfunction in offspring of diabetic rat dams. The pregnant Sprague Dawley (SD) rats (10) were randomly divided into the diabetic group (a single intraperitoneal injection of 35 mg/kg streptozotocin on day 0 of gestation) and control group (injected with the equal volume of 0.9% saline on day 0 of gestation) according to the random number table (5 each group).

Real-life time and distance covered by lay first responders alerted by means of smartphone-application: Implications for early initiation of cardiopulmonary resuscitation and access to automatic external defibrillators.

Aim Of The Study: To investigate the distance covered by lay first responders (LFR) alerted for an out-of- hospital cardiac arrest (OHCA), evaluate the time elapsed between mission acceptance and arrival at the OHCA site, as well as the distance between the LFRs to the closest automatic external defibrillator (AED).

Methods: The LFR route, thus time, distance information, and the average speed of each responder were estimated. The same methodology was used to calculate the distance between the closest AED and the LFRs, as well as the distance between the AED and OHCA site.

Irisin exerts a therapeutic effect against myocardial infarction via promoting angiogenesis.

Irisin, a myokine, is cleaved from the extracellular portion of fibronectin domain-containing 5 protein in skeletal muscle and myocardium and secreted into circulation as a hormone during exercise. Irisin has been found to exert protective effects against lung and heart injuries. However, whether irisin influences myocardial infarction (MI) remains unclear.

Reduced Cardio-Renal Function Accounts for Most of the In-Hospital Morbidity and Mortality Risk Among Patients With Type 2 Diabetes Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction.

Objective: ST-segment elevation myocardial infarction (STEMI) patients with type 2 diabetes mellitus (DM) have higher in-hospital mortality than those without. Since cardiac and renal functions are the main variables associated with outcome in STEMI, we hypothesized that this prognostic disparity may depend on a higher rate of cardiac and renal dysfunction in DM patients.

Research Design And Methods: We retrospectively analyzed 5,152 STEMI patients treated with primary angioplasty.

Sex And Prognostic Significance of Self-Reported Frailty in Non-ST-Segment Elevation Acute Coronary Syndromes: Insights From the TRILOGY ACS Trial.

Background: The effect of sex on self-reported frailty in acute coronary syndromes (ACS) is unclear. We examined the prevalence of self-reported frailty and its association with all-cause death among men and women.

Methods: Elderly (≥ 65 years) male (n = 2691) and female (n = 2305) patients with ACS enrolled in the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial were screened using the Fried Frailty Index.

Baseline Characteristics and Risk Profiles of Participants in the ISCHEMIA Randomized Clinical Trial.

Importance: It is unknown whether coronary revascularization, when added to optimal medical therapy, improves prognosis in patients with stable ischemic heart disease (SIHD) at increased risk of cardiovascular events owing to moderate or severe ischemia.

Objective: To describe baseline characteristics of participants enrolled and randomized in the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) trial and to evaluate whether qualification by stress imaging or nonimaging exercise tolerance test (ETT) influenced risk profiles.

Design, Setting, And Participants: The ISCHEMIA trial recruited patients with SIHD with moderate or severe ischemia on stress testing.

Validation of the return of spontaneous circulation after cardiac arrest (RACA) score in two different national territories.

Background: The likelihood of return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA) is influenced by unmodifiable (gender, aetiology, location, the presence of witnesses and initial rhythm) and modifiable factors (bystander CPR and the time to EMS arrival). All of these have been included in the ROSC After Cardiac Arrest (RACA) score.

Purpose: To test the ability of the RACA score to predict the probability of ROSC in two different regions with different local resuscitation networks: the Swiss Canton Ticino and the Italian Province of Pavia.